The primary objective of this proposal is to develop a novel electrospray ion source operating inside the mass spectrometer, based on internal heating of small droplets and water clusters. The use of internal heating (contrary to external one by ambient gas) of micro-droplets will allow using electrospray at reduced pressures inside the mass spectrometer. Such an introduction of ions will be much more efficient compared to conventional one which uses atmospheric pressure-vacuum interface. The efficient desolvation by internal heating, the absence of ion loss pertinent to conventional atmospheric pressure-vacuum interfaces, and elimination of the chemical noise originated from chemical impurities present in the ambient air are expected to substantially increase the sensitivity of the ESI-MS. PUBLIC HEALTH RELEVANCE: The application of mass spectrometry as a proteomics tool plays an important role in modern basic science, drug discovery and clinical applications. A novel electrospray ion source with enhanced sensitivity will further increase the speed and specificity of protein analysis.